MARCKS protein overexpression in inflammatory breast cancer
Autor: | Sinda Ayadi, Hamouda Boussen, Jeanne Thomassin-Piana, François Bertucci, Pascal Finetti, Maroua Manai, Amor Gamoudi, Jocelyne Jacquemier, Radhia Eghozzi, Khaled Rahal, Daniel Birnbaum, Max Chaffanet, Mohamed Manai, Marc Lopez, Olfa Ben Lamine, Emmanuelle Charafe-Jauffret, Patrice Viens |
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Přispěvatelé: | Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inst Carcinol Salah Azaiz Tunis, Institut Salah Azaiez de Cancer, Université de Tunis El Manar (UTM), Département de Biopathologie [Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Unité de Biochimie et Biologie Moléculaire [Tunis, Tunisie], Université de Tunis El Manar (UTM)-Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Service d’Oncologie Médicale [Tunis, Tunisie], Hôpital l’Ariana [Tunis, Tunisie], MITOYAN, Louciné, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU) |
Rok vydání: | 2016 |
Předmět: |
MARCKS
0301 basic medicine Oncology Pathology Time Factors [SDV]Life Sciences [q-bio] Kaplan-Meier Estimate 0302 clinical medicine Risk Factors Neoplasm Metastasis Myristoylated Alanine-Rich C Kinase Substrate skin and connective tissue diseases Aged 80 and over Middle Aged Up-Regulation 3. Good health Gene Expression Regulation Neoplastic [SDV] Life Sciences [q-bio] Treatment Outcome 030220 oncology & carcinogenesis immunohistochemistry Immunohistochemistry Female Inflammatory Breast Neoplasms France Research Paper Adult medicine.medical_specialty Poor prognosis Tunisia Adolescent [SDV.CAN]Life Sciences [q-bio]/Cancer Positive correlation survival Inflammatory breast cancer Disease-Free Survival Young Adult 03 medical and health sciences Breast cancer [SDV.CAN] Life Sciences [q-bio]/Cancer Internal medicine expression Biomarkers Tumor medicine Humans RNA Messenger Aged Neoplasm Staging Proportional Hazards Models Retrospective Studies Oncogene business.industry medicine.disease 030104 developmental biology Multivariate Analysis Neoplasm Grading inflammatory breast cancer business MARCKS Protein |
Zdroj: | Oncotarget Oncotarget, Impact journals, 2017, 8, pp.6246-6257. ⟨10.18632/oncotarget.14057⟩ Oncotarget, 2017, 8, pp.6246-6257. ⟨10.18632/oncotarget.14057⟩ |
ISSN: | 1949-2553 |
Popis: | // Maroua Manai 1, 5, 6, 7 , Jeanne Thomassin-Piana 2, * , Amor Gamoudi 6, * , Pascal Finetti 1, * , Marc Lopez 1 , Radhia Eghozzi 6 , Sinda Ayadi 6 , Olfa Ben Lamine 6 , Mohamed Manai 5 , Khaled Rahal 6 , Emmanuelle Charafe-Jauffret 2, 3 , Jocelyne Jacquemier 2 , Patrice Viens 3, 4 , Daniel Birnbaum 1 , Hamouda Boussen 5, 7 , Max Chaffanet 1 , Francois Bertucci 1, 3, 4 1 Departement d’Oncologie Moleculaire, Centre de Recherche en Cancerologie de Marseille, Aix Marseille Universite, Marseille, France 2 Departement de Bio-Pathologie, Institut Paoli-Calmettes, Marseille, France 3 UFR de Medecine, Aix Marseille Universite, Marseille, France 4 Departement d’Oncologie Medicale, Institut Paoli-Calmettes, Marseille, France 5 Departement de Biologie, Unite de Biochimie et Biologie Moleculaire, Faculte des Sciences de Tunis, Universite de Tunis El Manar, Tunisie 6 Departement d’Oncologie Medicale, Institut Salah Azaiez, Tunis, Tunisie 7 Service d’Oncologie Medicale, Hopital l’Ariana, Tunis, Tunisie * These authors contributed equally to second authors Correspondence to: Francois Bertucci, email: bertuccif@ipc.unicancer.fr Keywords: expression, immunohistochemistry, inflammatory breast cancer, MARCKS, survival Received: July 29, 2016 Accepted: December 14, 2016 Published: December 21, 2016 ABSTRACT Background: Inflammatory breast cancer (IBC) is the most aggressive form of locally-advanced breast cancer. Identification of new therapeutic targets is crucial. We previously reported MARCKS mRNA overexpression in IBC in the largest transcriptomics study reported to date. Here, we compared MARCKS protein expression in IBC and non-IBC samples, and searched for correlations between protein expression and clinicopathological features. Results: Tumor samples showed heterogeneity with respect to MARCKS staining: 18% were scored as MARCKS-positive (stained cells ≥ 1%) and 82% as MARCKS-negative. MARCKS expression was more frequent in IBC (36%) than in non-IBC (11%; p = 1.4E−09), independently from molecular subtypes and other clinicopathological variables. We found a positive correlation between protein and mRNA expression in the 148/502 samples previously analyzed for MARCKS mRNA expression. MARCKS protein expression was associated with other poor-prognosis features in the whole series of samples such as clinical axillary lymph node or metastatic extension, high pathological grade, ER-negativity, PR-negativity, HER2-positivity, and triple-negative and HER2+ statutes. In IBC, MARCKS expression was the sole tested variable associated with poor MFS. Materials and Methods: We retrospectively analyzed MARCKS protein expression by immunohistochemistry in 502 tumors, including 133 IBC and 369 non-IBC, from Tunisian and French patients. All samples were pre-therapeutic clinical samples. We searched for correlations between MARCKS expression and clinicopathological features including the IBC versus non-IBC phenotype and metastasis-free survival (MFS). Conclusions: MARCKS overexpression might in part explain the poor prognosis of IBC. As an oncogene associated with poor MFS, MARCKS might represent a new potential therapeutic target in IBC. |
Databáze: | OpenAIRE |
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